Elucidation of the relationship between SNAP-25 phosphorylation and stress disorder

Research Project

Project/Area Number	15K06778
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Neurochemistry/Neuropharmacology
Research Institution	Kitasato University
Principal Investigator	Yamamori Saori 北里大学, 医学部, 講師 (30464803)
Research Collaborator	TAKAHASHI Masami KODERA Yoshio Iida Yuuki
Project Period (FY)	2015-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000) Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000) Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	リン酸化 / シナプス / ストレス / SNAP-25 / 開口放出 / SNAREタンパク質 / 副腎
Outline of Final Research Achievements	Little is known about the molecular mechanisms in the brain, underlining stress adaptation. In this study, we aimed to elucidate the roles of SNAP-25 phosphorylation in this process. We found that: 1) SNAP-25 phosphorylation was elevated in the limbic system by stress stimulation; 2) in the areas where the SNAP-25 phosphorylation was elevated, monoamine release was increased; and 3) the SNAP-25 mutant mice in which Ser187 phosphorylation of SNAP-25 was specifically abolished exhibited reduced appetite under environmental stress conditions. These results suggest that the SNAP-25 phosphorylation in the brain induces stress adaptation and increases monoamine release and appetite.
Academic Significance and Societal Importance of the Research Achievements	ストレスはうつ病などの精神疾患の発症との関連が指摘されており、ストレスに対する適応機構の解明は医学的、社会的に喫緊の問題となっている。本研究では、脳内のSNAP-25のリン酸化が、ストレス刺激によるモノアミンの放出の増加に関わる可能性、摂食意欲の亢進に関与する可能性を見出した。これらの発見は、ストレスに対する反応および適応における分子制御機構の解明の一助になると考えられる。さらに、うつ病などの精神疾患の治療薬の開発のための基盤を提供する可能性がある。